Summary Background The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated ...precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. Methods Women (15–25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov , number NCT00122681. Findings Mean follow-up was 34·9 months (SD 6·4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92·9% (96·1% CI 79·9–98·3) in the primary analysis and 98·1% (88·4–100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30·4% (16·4–42·1) in the TVC and 70·2% (54·7–80·9) in the TVC-naive. Corresponding values against CIN3+ were 33·4% (9·1–51·5) in the TVC and 87·0% (54·9–97·7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54·0% (34·0–68·4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. Interpretation The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. Funding GlaxoSmithKline Biologicals.
Background Serum parathyroid hormone (PTH), phosphorus, and calcium levels are surrogate outcomes that are central to the evaluation of drug treatments in chronic kidney disease (CKD). This ...systematic review evaluates the evidence for the correlation between drug effects on biochemical (PTH, phosphorus, and calcium) and all-cause and cardiovascular mortality end points in adults with CKD. Study Design Systematic review and meta-analysis. Setting & Population Adults with CKD. Selection Criteria for Studies Randomized trials reporting drug effects on biochemical and mortality end points. Intervention Drug interventions with effects on serum PTH, phosphorus, and calcium levels, including vitamin D compounds, phosphate binders, cinacalcet, bisphosphonates, and calcitonin. Outcomes Correlation between drug effects on biochemical and all-cause and cardiovascular mortality. Results 28 studies (6,999 participants) reported both biochemical and mortality outcomes and were eligible for analysis. Associations between drug effects on surrogate biochemical end points and corresponding effects on mortality were weak and imprecise. All correlation coefficients were less than 0.70, and 95% credible intervals were generally wide and overlapped with zero, consistent with the possibility of no association. The exception was an inverse correlation between drug effects on serum PTH levels and all-cause mortality, which was nominally significant (−0.64; 95% credible interval, −0.85 to −0.15), but the strength of this association was very imprecise. Risk of bias within available trials was generally high, further reducing confidence in the summary correlations. Findings were robust to adjustment for age, baseline serum PTH level, allocation concealment, CKD stage, and drug class. Limitations Low power in analyses and combining evidence from many different drug comparisons with incomplete data across studies. Conclusions Drug effects on serum PTH, phosphorus, and calcium levels are weakly and imprecisely correlated with all-cause and cardiovascular death in the setting of CKD. Risks of mortality (patient-level outcome) cannot be inferred from treatment-induced changes in biochemical outcomes in people with CKD. Similarly, existing data do not exclude a mortality benefit with treatment. Trials need to address patient-centered outcomes to evaluate drug effectiveness in this setting.
Objective The ocular microflora in dogs has not been established in north-east Brazil. Thus, the main aim of this research was to determine the bacterial microorganisms in the conjunctival sac of ...clinically normal dogs and dogs with ulcerative keratitis in Fortaleza, Ceara, Brazil. Animals studied This study included 60 healthy dogs, 15 dogs with unilateral corneal ulcer, and three dogs with bilateral corneal ulcers. Procedure Samples were taken by a calibrated platinum loop (1 microliter) placed directly onto the conjunctival sac and on sterile blood agar. The clinical specimens were incubated at 37 degrees C in an atmosphere of 5% CO2 for 48 h. Results Of the 120 samples from healthy dogs, only 47 (39%) had positive culture for bacteria, while all of the specimens from eyes with corneal ulcer were positive for bacterial growth. The group of dogs with corneal ulcer had a higher (P < 0.05) number of colony-forming units (CFU) per plate than the group of healthy animals. Of the 59 isolates from healthy eyes, only nine (15.3%) had more than 50 CFU per plate, while in the group of dogs with corneal ulcer, 23 (62.2%) of the 37 isolates presented more than 50 CFU per plate. In both groups Gram-positive bacteria (86.5%) predominated over Gram-negative (13.5%). Staphylococcus spp. was the most frequently isolated genus and S. intermedius predominated in both groups. Conclusion The results of our study are directly applicable to initiate rational, preventive and therapeutic measures with greater accuracy in dogs with corneal ulcer.
Peritoneal dialysis (PD) patients may suffer changes in nutritional status after starting PD. Several markers can be used to evaluate these modifications, such as body mass index (BMI), serum ...albumin, and serum creatinine. Fluid overload should be considered because it can overestimate or underestimate nutritional status. The objective of this study was to evaluate the BMI changes over time in incident PD patients and identify interactions among BMI, signs of fluid overload, serum albumin, and serum creatinine.
The study included a cohort of 1,997 incident PD patients of the BRAZPD recruited from 2004 to 2007. Sociodemographic data and BMI classification were obtained at baseline. The evolutions of BMI and body weight were assessed over a period of 29 months. Changes in the evolution were analyzed when a patient presented with albumin < 3.8 g/dL, creatinine < 7.0 mg/dL, or the presence of edema. Data analysis was performed using linear mixed-effects regression models as the main statistical procedure.
BMI increased over time (29 months) by an average of 0.05 kg/m(2) per month, and body weight increased by 0.11 kg/month for a total increase of 3.08 kg. BMI decreased by 0.12 kg/m(2) in the presence of albumin < 3.8 g/dL and by 0.38 kg/m(2) in the presence of creatinine < 7.0 mg/dL. BMI increased by 0.61 kg/m(2) in the presence of edema. BMI increased in the presence of edema and albumin < 3.8 mg/dL or edema and creatinine < 7.0 mg/dL.
There is a mean increase in the BMI of incident PD patients over time, and these changes may be, at least partly, due to fluid overload, leading to distortions of body weight. When the patients presented with lower serum albumin or creatinine levels, the BMI values were reduced, suggesting that a reduction in lean mass and an increase in fat mass may be occurring in these patients.
Power quality is a matter of great concern for residential and commercial installation as well as for industry and electrical utilities. Taking into consideration the amount of lighting devices ...present in the above types of electrical systems, the investigation of their impact on power quality has become quite important. In this way, this paper studies the interaction between electronic and electromagnetic ballast fluorescent lamps and power quality. A combination of measurements and computer simulations using commercial types of devices is used. To illustrate the effect, an office building comprising nonlinear and linear loads, as well as different types of lighting is considered. The final harmonic distortion, active/reactive power loading, power factor, neutral current, etc are then analyzed for the two types of fluorescent ballast.
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